J. Org. Chem. 1991,56,6245-6248
6246
Scheme I'
Scheme IIa 0
0
0 b
C
c
*
0
7
8
10
11
12
13
14
15
'(a) AlCl,, CH,Cl,; (b) fuming HaO,; (c) aluminum cyclohexoxide, cyclohexanol. (0.222 mol) of KMn04 in portions (caution-frothing may occur) during a 40-min period, and the reaction mixture was refluxed for 3 h The reaction mixturewas allowed to cool somewhat and was fiitered. The collected solid (MnO?) was refluxed in water for 6 h and filtered while hot. The combined filtrates were evaporated in vacuo to one-half volume, cooled, and acidified slowly with concentrated HC1. The resulting solid was filtered and air-dried to give 12.20 g (70%) of white crystale with mp 281-283 OC (lit" mp 275 OC): IR (Nujol) 3312 (OH), 1743,1707, 1687,1655 ( C 4 ) cm-'; 'H NMR (CDSCOCDB)6 7.45-7.85 (m, 6 H), 9.47 (8, 1 H). Anthraquinone-2,3-dicarboxylicAcid (11). A solution of in 21 g of concentrated H#04 was triacid 10 (2.10 g, 6.69 "01) stirred and heated at 120 "C for 3 h and then poured onto 30 g of ice. The precipitate was filtered, washed with water, and air-dried to give 1.36 g (72%) of a pale yellow solid with mp >310 OC (lit?' mp 342 "C): IR (Nujol) 3166 (OH), 1638,1618 (C-0) cm-'; 'H NMR (CDsSOCDS)6 7.93-8.03 (m, 2 H), 8.20-8.30 (m, 2 H), 8.56 (8, 2 H). Anthracene-2,3-dicarboxylicAcid (12). To 50 mL of 20% NKOH were added sequencially 1.00 g (3.38 "01) of diacid 11 and then 3.75 g of activated zinc duet, and the blood-red mixture was refluxed. As soon as the color was discharged, the mixture was filtered while hot and the fiitered material was refluxed with 50 mL of 20% NH40H for 2 h. This mixture was filtered while hot and the combined filtrates were cooled to 0 OC and acidified to pH 1with 6 N HCl. The mixture was allowed to stand at room temperature for 1 day and then filtered to give 0.70 g (77%) of a bright yellow solid with mp >310 "C (lit.lemp 345 OC): IR (Nujol)3135 (OH), 1701,1674 (c--O)cm-';'H NMR (CD@CDd 6 7.55-7.70 (m, 2 H), 8.06-8.25 (m, 2 H), 8.49 (8, 2 H), 8.79 (8, 2
HI.
Dimethyl Anthracene-2,3-dicarboxylate(13). Into a refluxing mixture of diacid 12 (6.32 g, 23.8 mmol) in 80 mL of dry methanol was slowly passed HCl gas for 36 h. The mixture was cooled to 0 OC and filtered, and the colleded solid was dissolved in CH2Clp The solution was washed with 5% NaHCOS,dried over MgS04, and evaporated in vacuo to give 5.94 g (85%) of yellow solid with mp 149-151 OC (lit." mp 151 OC): IR (deposit) 1717 (M) cm-'; 'H NMR (CDCld 6 3.99 (s,6 H), 7.53-7.63 (m, 2 HI, 8.00-8.10 (m, 2 H), 8.44 (8, 2 H), 8.51 (8, 2 H). Chloro Thioether 14. Under nitrogen, a solution of diester 13 (0.85 g, 2.89 mmol) in 4 mL of dry DMSO and 5 mL of THF was added dropwise during a 15-minperiod to a stirred mixture of 0.35 g (8.75 mmol) of sodium hydride (60% dispersion in mineral oil) in 4 mL of dry DMSO and 2 mL of dry THF, and the mixture was stirred at room temperature for 12 h. The THF was removed in vacuo and the residual DMSO by a simple high vacuum distillation. The dark orange solid residue was diasolved in water (25 mL) and extracted with CH2C12(25 mL). The aqueous layer was added dropwise to 25 mL of 6 N HC1 during a 45-min period. The orange precipitate was fdtered and stirred for 3 h in 200 mL of CH2Clp The mixture was filtered and the filtrate was washed with water (2 X 100 mL), dried over MgSO,, and evaporated in vacuo. The residue was chromatographed on silica gel with CH2C12as eluent to give 0.30 g (33%) of a yellow-orange solid with mp 212 OC (dec): IR (deposit) 1736,1714 (C-0) cm-'; 'H NMR (CDCl,) 6 2.51 (8, 3 H), 7.61-7.74 (m, 2 HI, 8.05-8.18 (m, 2 H), 8.76 (a, 2 HI, 8.81 (8, 2 H). Anal. Calcd for C1&ClOpS: C, 66.16; H, 3.39. Found C, 66.40; H, 3.14. 0022-3263/91/ 1956-6245$02.50/0
(a) AICls, CH2C12;(b) HNO,; then KMnO,, aqueous NaOH (c) concd H,S04; (d) Zn, 20% NH40H (e) CH80H, HCI; (f) NaH, DMSO,T H F then HC1, H 2 0 (g) aqueous dioxane. Naphtho[flninhydrin (3).u C h l m thioether 14 (0.100 g, 0.30 mmol) was added in small portions during a 2-h period to a stirred solution of 9 mL of peroxide-free dioxane and 4 mL of distilled water at 95 "C. Heating was continued for 36 h and the reaction mixture was fdtered while hot. Dioxane was evaporated from the filtrate in vacuo, and 10 mL of water was added. The mixture was filtered and the collected solid was air-dried to give 0.068g (80%)of orange-red solid with mp 245 "C (de& IR (Nujol) 3331 (OH), 1741,1718 (Mm-'; ) 'H NMFt (CDSSOCDS) 6 7.59 (9, 2 H, OH), 7.70-7.80 (m, 2 H), 8.20-8.30 (m, 2 H), 8.90 (8, 2 H),9.05 (s,2 H). Anal. Calcds7for Cl7HBOS~0.4H2O C, 76.34; H, 3.32. Found C, 76.26; H, 3.66.
Acknowledgment. This research wss supported by United States Department of Justice, National Institute of Justice, grant number 87-IJ-CX-0030 to Professor E. Roland Menzel in the Department of Physics of Texas Tech University. Registry No. 4, 135989-72-9;6, 6321-58-0; 7, 53933-88-3; 8, 7258-46-0; 9, 52890-52-5; 10, 135989-69-4; 11, 27485-15-0; 12, 10210-28-3; 13, 56306-53-7; 14, 135989-70-7; 15, 135989-71-8; DMSO, 67-68-5; 1,4-cyclopentadienone,13177-38-3;2,3-bis(bromoethylbaphthalene, 38998-33-3; indane, 496-11-7; phthalic anhydride, 85-44-9; benzoyl chloride, 98-88-4; 1,2,4-trimethylbenzene, 95-63-6. (37)The formula C1,HBOais for the triketone formed by dehydration of 3. The elemental analysis sample waa dried for an extended period with heating in vacuo before submission for analysis and dried again in vacuo just prior to analysis.
Conjugated Polyene Synthesis via Disilyl Derivatives: A Direct Access to Ostopanic Acid, a Plant Anticancer Agent, and to (GE)-LTB, Leukotriene Francesco Babudri, Vito Fiandanese, and Francesco Naso* Centro C N R di Studio sulle Metodologie Innovative di Sintesi Organiche, Dipartimento di Chimica, Universitd di Bari, via Amendola 173, 70126 Bari, Italy Received April 30, 1991
Various classes of natural products such as alcohols,' aldehydes: ketones: and acids4 contain a conjugated 0 1991 American Chemical Society
Notes
6246 J. Org. Chem., Vol. 56, No. 21, 1991 Scheme I11
Scheme I
We3
Ib
Scheme I1 0
1)
MegSi
M I S ,CHzCIt, 0 "C
,, 2)
0 t
C -ICI
-SIM~~
la
-c1
6
0
0
T
C
,
C
4
Q
H
53% 6 (59%)
5 (54%)
AIC13. CH2C12 .O "C +rl 31 H I
polyene structure, with a specific double-bond geometry being a requirement of primary importance for biological activity. Thus, it is not surprising that considerable effort has been expended in seeking stereoselective methods for the synthesis of such conjugated systems. In continuation of our studies on the synthesis of stereodefined productss*6 such as alkenes6"or monoolefinic insect sex pheromones of E or 2 configuration,Bb1-silylated l,&dienes with a E,E or E,Z configuration,8dor pheromones with a conjugated (Z,E or E,Z) diene structureYhwe have recently reported a new approach to ketosilanes and dicarbonyl compounds with a conjugated (all E) diene or triene structure' (Scheme 1)* The highly chemoselective substitution of one trimethylsilyl group of la (n = o), (lE,3E)-l,4-bis(trimethylsily1)-l,&butadiene,or lb (n = 11, (1E,3E,5E)-1,6bis(trimethylsilyl)-l,3,bhexatriene, with acyl chlorides in the presence of AlC13 afforded silylated ketones 2. Subsequent substitution of the second silyl group with another acyl chloride in the same reaction flask led to the diketone derivatives 3. Both compounds 2 and 3 present several interesting features owing to the possibility of elaborating the silicon and/or the carbonyl functionality for further transformations. Indeed, with this procedure, one may envisage a number of syntheses of natural compounds with a polyene structure. With the aim of illustrating the versatility of our approach and the highly efficient synthetic potential of the disilyl derivatives la and lb, we now report their successful use in the synthesis of a series of polyunsaturated fatty acids of special interest. (1) Hirai, N.; Kingston, D. G.I.; Van Tassell, R. L.; Wilkins, T. D. J. Am. Chem. SOC. 1982,104,6149. Nicolau, K. C.; Zipkin, R.; Tanner, D. J. Chem. SOC., Chem. Commun. 1984, 349. Pfaendler, H. R.; Maier, F. 1986,108,1338. Vertegaal, L. B. J.; van K.; Klar, S . J. Am. Chem. SOC. der Gen, A. Tetrahedron 1990,46, 7301. (2) Bohlmann, F.; Czerson, H. Chem. Ber. 1976,109, 2291. (3) Sleeper, H. L.; Fenical, W.J. Am. Chem. SOC.1977,99,2367. Shi, L.; Xia, W.; Yang, J.; Wen, X.; Huang, Y. 2. Tetrahedron Lett. 1987,28, 2155. Ma, D.; Yu, Y.; Lu, X. J. Org. Chem. 1989,54,1105. Cimino, C.; Spinella, A.; Sodano, G. Tetrahedron Lett. 1989,30,5003. Duhamel, L.; Ple, G.; Ramondenc, Y. Tetrahedron Lett. 1989,30,7377. (4) Cason, J.; Davis, R.; Sheehan, M. H. J. Org.Chem. 1971,36,2621. Hayashi, T.; Oishi, T. Chem. Lett. 1985,413. Bloch, R.; Perfetti, M.-T. Tetrahedron Lett. 1990, 31, 2577. Kann, N.; Rein, T.; Akermark, B.; Helquist, P. J. Org. Chem. 1990,55, 5312. (5) For reviews, see: Naso, F. Pure Appl. Chem. 1988,60,79. Fiandanese, V. Pure Appl. Chem. 1990,62, 1987. (6) (a) Fiandanese, V.; Marchese, G.;Naso, F.; Ronzini, L. J. Chem. Soc., Chem. Commun. 1982,647. (b) Fiandanese, V.; Mnrchese, G.;Naso, F.; R o d , L. J. Chem. Soc., Perkin !Duns.1, 1985,1115. (e) Fiandaneae, V.; Miccoli, G.;Naso,F.; Ronzini, L. J. Organomet. Chem. 1986,312,343. (d) Fiandanese, V.; Marchese, G.;Mascolo, G.;Nam, F.; Ronzini, L. Tetrahedron. Lett. 1988, 29, 3705. (e) Fiandanese, V.; Marchese, G.; Naso, F.; Ronzini, L.; Rotunno, D. Tetrahedron Lett. 1989, 30, 243. (7) Babudri, F.; Fiandaneae, V.; Marcheee, G.;Naso, F. J. Chem. Soc., Chem. Commun. 1991, 237.
COOMe COOMe
1(30%) OH
9 (87%)
+ OH
8 (46%)
COOH
11 (46%)
OH COOH
10 (53%)
Ostopanic acid (4), a cytotoxic fatty acid, recent19 isolated in minute quantity (0.009%)from the stem and fruits of Ostodes paniculata Blume (Euphorbiaceae), has been shown to inhibit the growth of P-388lymphocytic leukemia test system in vitro. To date, only one reportg has described the total synthesis, in low yield and in several steps, of this natural product. The interesting biological activity and the E$-dienyl diketone structure of this compound led us to devise a simple synthetic strategy based upon our procedure. Indeed, as outlined in Scheme 11, the synthesis of ostopanic acid was conveniently achieved by a one-pot procedure by adding, in the first step, a dichloromethane solution of the heptanoyl chloride-AlCl, complex to an equimolar amount of la. After completion of the first step and without isolation of the monosubstitution product, a solution of the pimeloyl dichloride-AlC1, complex was added, leading to compound 4 with an overall 53% yield. Furthermore, in view of the ease of preparation of 1,6diacylhexatrienes, illustrated above in Scheme I, the synthetic route appeared to be suited ideally to the construction of the 6E isomerlo and structural analogues" of leukotriene B3,which, in recent years, for its chemotactic activity, has attracted a reat deal of attention from the synthetic point of view.1E14 As depicted in Scheme 111, (8) Hamburger, M.; Handa, S. S.; Cordell, G. A.; Kinghom, A. D.; Farnsworth, N. R. J. Nat. Prod. 1987,50, 281. (9) Sheu, J.-H.; Yen, C.-F.; Huang, H.-C.; Hong, Y.-L. V. J. Org. Chem. 1989,54,5126. (10) Wenkert, E.; Guo, M.; Lavilla, R.; Porter, B.; Ramachnndran, K.; Sheu, J.-H. J. Org. Chem. 1990,55,6203. (11) Nakamwa, T.; Namiki, M.; Ono, K. Chem. Phurm. Bull. 1987,35, 2635. (12) Spur, B.; Crea, A.; Peters, W. Arch. Pharm. (Weinheim) 1986, 318, 225. (13) Guillerm, D.; Linstnunelle, G. Tetrahedron Lett. 1986,27,5857. (14) Kobayashi, Y.; Shimazaki,T.; Taguchi, H.; Sato, F. J. Org.Chem. 1990,55, 5324. (15) Separation of these diastereomers has been reported in ref 10.
Notes
J. Org. Chem., Vol. 56, No. 21, 1991 6247
the l,&diacyl 1,3,5-triene systems 5 and 611were accessible by the same one-pot procedure, starting from compound lb and employing the appropriate acyl chlorides in the two steps. Finally, completion of the synthesis required borohydride reduction of diketo esters 5 or 6 to give the intermediate dihydroxy esters 7 or 9, whose mild alkaline hydrolysis led to (GE)-leukotriene B3 (11)'O or to structurally related 10, both as a diastereomeric mixture. It is worth noting that the reduction of compound 5 led to the intermediate dihydroxy ester 7 and to the related y l a h n e 8, whose hydrolysis gave the same product 10. In conclusion, we believe that the present method, providing an easy and direct access to polyunsaturated fatty acids of special interest, compares very favorably with alternative procedures. Further extension of our methodology to the synthesis of natural products possessing a tetraene or pentaene structure is currently in progress. Experimental Section All the acyl chlorides were commercially available (Aldrich). Merck silica gel (60,particle size 0.040-0.063 mm) was used for flash column chromatography. High performance liquid chromatography (HPLC) was performed on a Partisil-10 PAC (Whatman) column (4.6mm X 25 cm). GC analyses were performed with a SPB-1(methylsilicone, 30 m x 0.25 mm i.d.) capillary column. 'H NMR data were measured at 200 MHz and lacNMR data at 50.3 MHz on a Varian XL 200 spectrometer. NMFl spectral data taken in CDC13used the residual CHC&singlet a t 6 7.26 as the standard for 'H data and the triplet centered at 6 77.0 as the standard for '9c spectra. In cases where the sample did not dissolve completely in deuteriochloroform, a few drops of deuterated dimethyl sulfoxide were added to achieve a homogeneous solution. Ostopanic Acid (4). A CHzClz solution (10mL) of freshly distilled heptanoyl chloride (0.83 g, 5.6 mmol) was added, under nitrogen, to a cold (0 "C) stirred suspension of anhydrous AlC13 (0.74g, 5.6 "01) in 10 mL of CH2C12. The resulting mixture was allowed to stir at 0 "C for 10 min. The obtained clear solution was transferred via syringe to the addition funnel of a threenecked flask,equipped with a magnetic stirrer, and cooled at 0 OC, under nitrogen, which contained a CH2C12 solution (10mL) of la (1g, 5 "01). After complete addition at 0 "C, the mixture was stirred at the same temperature and the reaction was monitored by capillary GC analysis. After reaction completion (4h), a solution (20mL) of the pimeloyl dichloride-A1C13 complex, prepared as described above from 1.42 g (7.2mmol) of pimeloyl dichloride and 2 g (15mmol) of AlC13,was dropped at 0 "C under nitrogen. After the addition, the reaction mixture was slowly brought at room temperature, stirred for 1.5 h, the time required for completion, quenched with saturated aqueous NH4C1, and extracted with ether. The organic extracts were washed with water, dried over Na2S04, and concentrated to give a solid product. Recrystallization from ether gave 0.82g (53% overall yield) of ostopanic acid (4): mp 132-133 OC (lit? mp 132-133 "C). The 'H and lacNMR spectral data were in agreement with those reported.s*@ Methyl 4,l l-Dioxo-5(E),7(E),S(E)-nonadecatrienoate(5). Following the same procedure described for the synthesis of ostopanic acid, compound 5 was prepared starting from l b (1g, 4.5 mmol) and using 4.9 mmol of the nonanoyl chloride-A1C13 complex (nonanoyl chloride 0.87 g, AlC13 0.65 g) (1h, reaction time) in the first step and the complex deriving from methyl (1.5 succinyl chloride (1g, 6.7 mmol) and AlC13(1.8g, 13.5 "01) h, reaction time) in the second step. After the usual workup, flash chromatography on silica gel of the residue (elution with 9.50.5 methylene chloriddiethyl ether) afforded 0.81 g (54%) of 5: mp 112-113 "C (from EtOH) (lit." mp 108.5-109 "C). The lH N M R spectrum was in agreement with that reported." Methyl 4,l I-Dihydroxy-S(E),7(E),S(E)-nonadecatrien~te (7)and 7-Lactone 8. A mixture of diketo eater 5 (0.8 g, 2.4 "01) and NaBH4 (0.2g, 5.3 mmol) in 40 mL of MeOH was stirred at 0 "C. After reaction completion (2h), the solvent was evaporated and dilute aqueous hydrochloric acid was added. Then the mixture was extracted with methylene chloride, dried, and
evaporated. Flash chromatography of the residue (elution with 7:3 methylene chloride-diethyl ether) yielded 0.34 g (46%) of y-lactone 8 as a 1:l mixture of diastereomers WLC,hexane-ethyl acetate 6:4,t~ 15.1,16.6min, flow rate = 1 mL/min), mp 65-69 "C (from EhO/hexane): IR (KBr) 3344,1772,1648,999cm-'; 'H NMR (CDC13 + DpO) 6 0.84 (t,J = 6.4 Hz, 3 H), 1.10-1.62 (m, 14 H), 1.86-2.08 (m, 1 H), 2.28-2.60 (m, 3 H), 4.06-4.22 (m, 1 H), 4.90-5.04 (m, 1 H), 5.58-5.84 (m, 2 H), 6.08-6.42 (m, 4 H); I3C NMR (CDClS) 6 14.1,22.6,25.3, 28.5,28.8, 29.2, 29.5, 31.8, 37.2,72.5,80.4,129.7,130.8,132.9,134.2,138.0,176.9. Anal. Calcd for Cl&O3: C, 74.47;H, 9.87. Found C, 74.65; H, 9.93. Further elution gave 0.24 g (30%) of compound 7 as a mixture (1:l)of the two diastereomers (HPLC, hexane-ethyl acetate 7:3, t~ 19.8, 22.9 min, flow rate = 1 mL/min), mp 68-71 "C (from EhO/hexane): IR (KBr) 3305,1737,1639,989cm-'; 'H NMR (CDC13+ DzO) 6 0.84 (t,J = 6.3 Hz, 3 H), 1.10-1.60 (m, 14 HI, 1.74-1.92 (m, 2 H), 2.39 (t, J = 7.3 Hz,2 H), 3.63 (a, 3 H), 4.02-4.30 (m, 2 H), 5.55-5.80 (m, 2 HI, 6.05-6.35 (m, 4 H);'SC NMR (CDCld 6 14.1,22.6,25.4,29.2,29.5,30.0,31.8, 37.3,51.7,71.6,72.6,130.1, 130.7,131.9,132.6,135.4, 136.9,174.3. Anal. Calcd for C&%04: C, 70.97;H, 10.12. Found C, 71.10; H, 10.28. 4,l l-Dihydroxy-5(E),7(E),S(E)-nonadecatrienoic Acid (10). Compounds 7 and 8 were separately hydrolyzed as follows: 2 mL of a 0.36 M lithium hydroxide aqueous solution (0.72mmol) was added to a THF solution (5 mL) of the dihydroxy ester 7 (0.24 g, 0.71 mmol) and the mixture was stirred at 0 "C for 1 h, neutralized with dilute aqueous hydrochloric acid, and extraded with CH2C12. The extract was washed with water and dried over Na2SOI. Evaporation of the extract followed by crystallization yielded 0.11g of compound 1 0 mp 102-104 "C (from CH2C12/ EhO); IR (Nujol) 3301,3222, 1709, 1680, 988 cm-'; 'H NMR (CDCla + D20, trace DMSO-de) 6 0.69 (t, J = 6.4 Hz, 3 H), 0.95-1.50 (m, 14 H), 1.55-1.75 (m, 2 H), 2.21 (t,J = 7.4 Hz, 2 H), 3.87 (4, J = 6.3 Hz, 1 H), 3.99 (9,J = 6.3 Hz, 1 HI, 5.40-5.65 (m, 2 H), 5.92-6.20 (m, 4 H), I3C NMR (CDCla, trace DMSO-de) 6 13.6,22.0, 24.9,28.6,28.9, 29.0,29.7,31.2,31.6,36.9,70.3,71.3, 12892,128.95(diastereomer), 129.38,129.41(diastereomer),131.1, 131.7,135.8,137.1,175.3. Anal. Calcd for Cl&820,: C, 70.33;H, 9.94. Found: C, 70.08; H, 10.06. The hydrolysis of compound 8 was performed in a similar manner, starting from 0.34g (1.11mmol) of 8 and 1.11 mmol of LiOH solution (3mL, 0.37 M), leading, after crystallization, to 0.20 g of 10. Taking also into account the amount (0.11g) of compound 10 deriving from the hydrolysis of compound 7,the overall yield was 53% Methyl 5,12-Dioxo-6(E),8(E),lO(E)-eicosatrienoate (6). Compound 6 was prepared as described for compound 5, starting from 4.5 mmol of lb and using the complex deriving from methyl glutaryl chloride (1.1g, 6.7 mmol) and AICla (1.8g, 13.5 mmol) in the second step. Flash chromatography of the residue afforded 0.92 g (59%) of 6: mp 126-127 "C (from EtOH) (lit." mp 122-122.5 "C). The spectral data ('H and 13C NMR) were in agreement with those reported.lOJ1 Methyl 5,12-Dihydroxy-6(E),8(E),10(E)-eicosatrienoate (9). Sodium borohydride reduction of diketo ester 6 (0.5 g, 1.43 mmol) yielded 91° (0.44g, 87%) as a waxy residue, sufficiently pure for further reaction, as evidenced by HPLC (99% chemical purity, a mixture 1:l of diastereomers, ethyl acetatehexane 1:l as eluent, tR 10.9, 12.9 min, flow rate = 1 mL/min).ls 'H NMR (CDC13+ D20) d 0.85 (t,J = 6.4 Hz, 3 H), 1.12-1.42 (m, 12 H), 1.45-1.82 (m, 6 H), 2.33 (t, J = 7 Hz, 2 H), 3.64 (s, 3 H),4.03-4.20 (m, 2 H), 5.55-5.85 (m, 2 H), 6.10-6.40 (m, 4 H). (6E)-LTBS(11). After alkaline hydrolysis of compound 9 (0.43 g, 1.22 m o l ) with an LiOH solution and usual workup, the residue was purified by crystallization, and 0.19 g of 11'O (46%) was obtained: mp 101-103 "C (from CHpC12/EhO);'H NMR (CDCla + DzO, trace DMSO-& d 0.80 (t, J = 6.3 Hz, 3 H),1.10-1.35 (m, 12 H), 1.40-1.75 (m, 6 H), 2.25 (t, J = 7.3 Hz, 2 H), 3.95-4.15 (m, 2 H), 5.52-5.75 (m, 2 H), 6.03-6.30 (m, 4 H).
.
Acknowledgment. This work was supported by the National Research Council of Italy (C.N.R.), Progetto Finalizzato Chimica Fine 11.
J. Org.Chem. 1991,56,6248-6250
6248
RegiBtry No. la,22430-47-3;lb,133683-82-6,4,110187-19-4; 6,104226-70-2;6,114730-22-2; 7 (ieomer l),135570-106;7 (homer 2),135570-11-5;8 (isomer l),135570-12-6;8 (isomer 2), 13557013-7;9 (isomer l), 135570-16-0;9 (isomer 2), 135570-17-1;10 (isomer l),135570-14-8;10 (isomer 2), 135570-15-9;11 (isomer 11, 135637-50-2;11 (isomer 2), 135637-51-3;H3C(CHp)COCl, 334-19-0;ClCO(CH&COCl, 142-790;H&(CHJ&OCl, 764-85-2; MeO2CCH2CH2COC1, 1490-25-1;MeO2C(CH2)COC1,1501-26-4.
Soheme Io
3
4
Organic Reactions Catalyzed by Solid Superacids. 10.' Perfluorinated Sulfonic Acid Resin (Nafion-H) Catalyzed Ring Closure Reaction of 23-Diaminobiphenyls. A Preparative Route to Carbazoles Takehiko Yamato,*J Chieko Hideshima,' Kazuaki Suehiro,' Masashi Tashiro? G. K. Surya Prakash) and George A. Olah* Department of Industrial Chemistry, Faculty of Science and Engineering, Saga University, Honjo-machi, Saga 840, Japan, Research Institute of Advanced Material Study, Kyushu University, 6-1, Kasuga-kohen, Kasuga-shi, Fukuoka 816, Japan, and Donald P.and Katherine B. Loker Hydrocarbon Research Institute and Department of Chemistry, University of Southern California, University Park, Los Angeles, California 90089-1661 Received May 3,1991
Introduction The acid-catalyd ring closure of 2,2'-diaminobiphenyls to corresponding carbazoles has been studied using various acids.2-' However, these methods require elevated temperatures (>200 "C),long reaction times, and excess of protic acids. Furthermore, some of these reactions were plagued with undesirable side products during cyclization.' Therefore, the scope and selectivity for the preparation of carbazole derivatives have been limited. Recently, we have found that Nafion-H, a perfluorinated sulfonic acid resin, catalyzes ring closure of 2,2'-dihydroxybiphenyls to dibenzofuran derivatives under relatively mild condition^.^ Now we wish to report an efficient and mild procedure for the ring closure of 2,2'-diaminobiphenyls in the presence of the solid superacid, Ndion-H, to afford carbazole derivatives in good to moderate yields. Results and Discussion The preparative route for 2,2'-diamino-4,4'dibromobiphenyl (IC), 2,2'-diamino-3,3',5,5'-tetramethyl-4,4'-dimethoxybiphenyl (ld), and 2,2'-diamino-4,4',5,5/-tetramethoxybiphenyl (le) is shown in Scheme I, and the preparation of other diaminobiaryls la and lb was carried out by the reduction of the corresponding dinitrobiaryls with Sn-HCl in ethanol according to the literature.The attempted ring closure reaction of 4,4'-di-tert-butyl-2,2'-diaminobiphenyl (lb),performed in refluxing oxylene for 36 h in the presence of Nafion-H, failed. Only starting material was recovered. However, when the reaction was carried out in refluxing 4-tert-butyltoluene, 4-tert-butyl-o-xylene,or nitrobenzene, the desired product, 2,7-di-tert-butylcarbazole (2b),was obtained (Table I). In the case of 4-tert-butyltoluene reflux, it takes more than 36 h to complete the reaction, but under 4-tert-butyl-oxylene or nitrobenzene reflux only 12 h are required. +Saga University. t Kyushu University. 1 University of Southern
California.
0022-3263/91/1956-6248$02.60/0
7
--
a; R' -OM.F?.R'. b; R'
RZ OM, RS
~e H
I
"Key: (i) Cu/DMF, 120 OC for 1 h; (ii) Sn/HCl/EtOH; (iii) NiCls/Zn/triphenylphoephine/DMF', 50-60 OC for 12 h; (iv) Cu, 260 "C for 3 h; (v) fuming HNOB/AqO. Table I. Nafion-H-Catalyzed Condenrotion of 4,4'-Di-tert-butyl-2f'-~nobiphenylrlb NH2
Nafion-H Ar-H reflux H
lb
2b
amount of Nafon-H reaction run solvent (wt%) time(h) lb 2b 1 o-xylene 36 100 0 50 50 12 41 54 2 4-tert-butyltoluene 100 12 35 61 3 4-tert-butyltoluene 4 4-tert-butyltoluene 100 48 0 98 (Wb 5 4tert-butyl-o-xylene 50 12 5 9 0 6 4tert-buty1.0-xylene 50 12 4 90 (87)b 7 nitrobenzene 50 12 0 96 (93Y o o d 8 biphenyl' 100 12 "Yieldsme determined by GLC analyses. bIsolatedyields are shown in parentheses. cReaction temperature: 250-260 OC. dCarbazole 2. was obtained in quantitative yield.
However, when nitrobenzene was used as a solvent, the highest isolated yield of 2b (run 7) was obtained, but a remarkable deactivation of catalyst was observed because regeneration of catalyst could not be achieved to the original catalytic activity. Product 2b was isolated by simple filteration of the hot reaction mixture followed by distillation of the filtrate. (1) Organic Reactions Catalyzed by Solid Superacids. 10. Part 9 Yamato. T.; Sakaue, N.: Tashiro. M.: Prakash, G. K. S.; Olah, G. A. d. Chem. Res., Miniprint, in press. (2)THuber, E.Ber. Dtsch. Chem. Gee. 1891,24,200. (3)Lediteke. H. Ber. 1953,86,522. (4) Tashiro, M.;Fukuda, Y.; Yamato, T. Heterocycle8 1081,16,771. (5) Yamato, T.; Hideshima, C.; Prakeeh, G. K. S.; Olah, G.A. J. Org. Chem. 1991,56,3192. (6)Corbett, J. F.;Holt, P. F. J. Chem. SOC.1960,3646. (7)Tashiro, M.;Yamato, T. Synthesis 1979,48. (8)Tashiro, M.;Yamato, T. J. Org. Chem. 1979,44,3037.
Q 1991 American Chemical Society
